Abstract
Generation of induced pluripotent stem cells by defined factors has become a useful model to investigate the mechanism of reprogramming and cell fate determination. However, the precise mechanism of factor-based reprogramming remains unclear. Here, we show that Klf4 mainly acts at the initial phase of reprogramming to initiate mesenchymal-to-epithelial transition and can be functionally replaced by bone morphogenetic proteins (BMPs). BMPs boosted the efficiency of Oct4/Sox2-mediated reprogramming of mouse embryonic fibroblasts (MEFs) to ∼1%. BMPs also promoted single-factor Oct4-based reprogramming of MEFs and tail tibial fibroblasts. Our studies clarify the contribution of Klf4 in reprogramming and establish Oct4 as a singular setter of pluripotency in differentiated cells.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Bone Morphogenetic Proteins / metabolism*
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Bone Morphogenetic Proteins / physiology
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Cellular Reprogramming*
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Fibroblasts / cytology*
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Homeodomain Proteins / metabolism
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Induced Pluripotent Stem Cells / metabolism
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Kruppel-Like Factor 4
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Kruppel-Like Transcription Factors / metabolism*
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Kruppel-Like Transcription Factors / physiology
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Lewis X Antigen / metabolism
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Mice
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Mice, Transgenic
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Nanog Homeobox Protein
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Octamer Transcription Factor-3 / metabolism*
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Octamer Transcription Factor-3 / physiology
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Transcription Factors / metabolism
Substances
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Bone Morphogenetic Proteins
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Homeodomain Proteins
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Klf4 protein, mouse
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Kruppel-Like Factor 4
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Kruppel-Like Transcription Factors
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Lewis X Antigen
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Nanog Homeobox Protein
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Nanog protein, mouse
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Octamer Transcription Factor-3
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Zfp42 protein, mouse
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Transcription Factors